Ventilator associated pneumonia (VAP) is a potentially preventable cause of pneumonia that occurs in patients who are endotracheally intubated and mechanically ventilated for more than 48 hours. VAP may occur in up to 65% of patients in the intensive care unit (ICU) and is associated with an increase in morbidity and mortality. It is estimated that cost of diagnosing and treating VAP exceeds 1.1 billion dollars annually. Young P J, Ridley S A, Ventilator-associated pneumonia, Diagnosis, pathogenesis and prevention, Anaesthesia 1999; 54(12):1183-97; Morehead R S, Pinto S J, Ventilator-associated pneumonia, Arch Intern Med 2000; 160(13):1926-36.
VAP is usually a bacterial nosocomial pneumonia, which was neither present nor incubating at the time of endotracheal intubation. Causes of VAP are multifactorial (FIG. 1). The diagnosis of VAP is difficult and expensive. Controversy continues to exists in the methodology in making a definitive diagnosis. Treatment is also controversial and the use of empiric antibiotics is believed to have contributed to making the overall treatment of true VAP more difficult. Patients developing VAP require additional testing to make the diagnosis and additional treatments. A major cost to the treatment is prolonging the time patients require mechanical ventilation and thus care in the ICU setting. This increased time of treatment in this setting is likely to actually increase the chances of additional complications including developing additional VAPs and antibiotic resistant organisms.
The microbiology of VAP consist of a combination of Gram positive, Gram negative, and anaerobic organisms, most of which are ororpharyngeal or enteric in origin. As such a major mechanism believed to be responsible for the development of VAP is the microaspiration of pooled oropharyngeal secretions around the inflated cuff of an endotracheal tube (FIG. 2).
Despite the use of high volume low pressure (HVLP) endotracheal tube cuffs, there is clear evidence that small channels develop between the endotracheal tube cuff and the trachea, which allow passage of subglottic secretions into the lower respiratory tract. These channels develop because small folds develop from incomplete expansion of the endotracheal tube cuff. Seegobin R D, van Hasselt G L, Aspiration beyond endotracheal cuffs, Can Anaesth Soc J 1986; 33(3 Pt 1):273-9. The number of the folds or channels can be reduced if higher volumes are used to inflate the cuffs. However, higher volumes will result in higher pressures being created between the cuff and the tracheal mucosa thus placing the tracheal mucosa at risk for necrosis.
One strategy to reduce VAP from pooled secretions has been to perform continuous aspiration of subglottic secretions (CASS). A specially designed endotracheal tube called the HI-LO® EVAC tube by Mallinckrodt allows for this. This endotracheal tube contains a separate dorsal lumen ending in the subglottic space just above HVLP cuff. Fluid can be drained along this channel with suction. When clinically studied, the incidence of VAP has been reduced from 29% to 13% with intermittent drainage and 32% to 18% with continuous drainage. (Valles J, Artigas A, Rello J, Bonsoms N, Fontanals D, Blanch L, et al., Continuous aspiration of subglottic secretions in preventing ventilator-associated pneumonia, Ann Intern Med 1995; 122(3):179-86; Kollef Skubas N J, Sundt T M, A randomized clinical trial of continuous aspiration of subglottic secretions in cardiac surgery patients, Chest 1999; 116(5):1339-46.) The method appears to result in major cost savings if its use were wide spread. (Shorr A F, O'Malley P G, Continuous Subglottic Suctioning for the Prevention of Ventilator-Associated Pneumonia: Potential Economic Implications, Chest 2001; 119:228-35.) The disadvantage of this method is that suction is required. Because endotracheal intubation occurs in many non-ICU areas, suction is not readily available. Patients are likely to be a most risk for aspiration from subglottic secretions very early after intubation especially when it is performed in less than ideal places such as on the wards, the emergency department, or in the prehospital setting. For example, over 55% of head-injured patients requiring intubation in the field or emergency department development pneumonia which might be from very early aspiration. (Livingston DH, Prevention of ventilator-associated pneumonia, Am J Surg 2000; 179(2A Suppl):12S-17S.) Furthermore, patients often require movement from the ICU to other locations within the hospital in order to undergo additional treatments or diagnostic studies. Continuous suction may not be available during these times. In addition, maneuvers such as changing patient position in a bed may serve to increase balloon channel size or relationship between the HI-LO EVAC port and the pooled secretions thus creating additional opportunity for aspiration.
A number of methods, which involve changes in cuff design, have reported various degrees of success but none have undergone extensive clinical testing. One method has used a latex cuff, which appears to provide the sealing effectiveness of low volume high pressure cuffs without damage to the tracheal wall. (Young P J, Ridley S A, Downward G., Evaluation of a new design of tracheal tube cuff to prevent leakage of fluid to the lungs, Br J Anaesth 1998; 80(6):796-9.) The addition of keeping the cuff at a constant pressure using a special inflation system adds to the degree of protection. (Young P J, Basson C, Hamilton D, Ridley S A, Prevention of tracheal aspiration using the pressure-limited tracheal tube cuff, Anaesthesia 1999; 54(6):559-63.) A modification of this cuff using silicone has been studied in humans requiring tracheostomy and appears to decrease leakage of supraglottic fluid compared conventional HVLP cuffs. (Young P J, Burchett K, Harvey I, Blunt M C, The prevention of pulmonary aspiration with control of tracheal wall pressure using a silicone cuff, Anaesth Intensive Care 2000; 28(6):660-5.) This tube and cuff are manufactured by Euromedical Industries and have been used as part of the intubating laryngeal mask system.
Another cuff called the Portex Soft Seal HVLP cuff (Portex Ltd, Hythe UK) has been tested against other HVLP cuffs in bench models and appears to perform better in terms of reducing leakage around the cuff. (Young P J, Blunt M C, Compliance characteristics of the Portex Soft Seal Cuff improves seal against leakage of fluid in a pig trachea model, Crit Care (Lond) 1999; 3(5):123-26.)
Also a unique thin walled endotracheal tube has been designed in which a traditional air filled cuff is replaced by a series of circumferential gills. During intubation, the tube is placed so that a number of the gills are above and below the vocal cords. This creates a seal for positive pressure ventilation (up to 40 cm H2O of peak inspiratory pressure) as well as a barrier to supraglottic secretions. (Reali-Forster C, Kolobow T, Giacomini M, Hayashi T, Horiba K, Ferrans V J, New ultrathin-walled endotracheal tube with a novel laryngeal seal design: Long-term evaluation in sheep, Anesthesiology 1996; 84(1):162-72; discussion 27A.) Although tested in animals we are not aware of any clinical testing. It is unknown what type of reaction might be caused by the gills coming in contact with the vocal cords in terms of irritation.
Other device strategies to reduce or prevent VAP have been to embed the endotracheal tube with antimicrobials such as silver. This method appears to reduce the bacterial load. (Hartmann M, Guttmann J, Muller B, Hallmann T, Geiger K, Reduction of the bacterial load by the silver-coated endotracheal tube (SCET), a laboratory investigation, Technol Health Care 1999; 7(5):359-70) However, it is presumed that the secretions must be in contact with the silver for sufficient periods of time for its antimicrobial activity to be effective. In regards to this, intubation done in less than ideal circumstances where patients may be at greatest risk for microaspiration means that antibiotic embedded systems or tubes designed to prevent formation of biofilm might not be effective in this time early time range.
Another major problem in the patient requiring endotracheal intubation and mechanical ventilation is the need for sedation due to the coughing reflexes induced by contact of the endotracheal tube and cuff with points of the supra and subglottic portions of the larynx. These points include the epiglottis, vocal cords, and tracheal mucosa. These reflexes are capable of producing such irritation and coughing as to require significant systemic sedation. This degree of additional sedation can impede physical and neurologic assessment of the patient and delay efforts for weaning of mechanical ventilation. This is of great importance because additional time spent utilizing mechanical ventilation will necessarily result in the incurrence of significant expense and may potentially result in the development of VAP with all of its complications and additional expense.
Methods/devices used to reduce the coughing reflex associated with endotracheal tubes include instilling local anesthetics through the lumen of the endotracheal tube. This method is believed to anesthetize to carina of the tracheal-bronchial tree. One device was found on the interne, which depicts a multilumen endotracheal tube allowing for instillation of anesthetic agents such as lidocaine. These ports appear to end at various locations along the tracheal bronchial tree. It is assumed that intermittent administration and contact of anesthesia at these points will provide sufficient anesthesia of the tracheal bronchial tree in contact with the endotracheal tube as to significantly blunt the coughing reflex.
Patent literature about prevention and/or reduction of ventilator associated pneumonia is as follows.
U.S. Patent Application No. 20030073625 was published Apr. 17, 2003, by Redman et al., for “Methods of preventing ventilator associated pneumonia by oral administration of antimicrobial IB-367 peptides.”
U.S. Patent Application No. 20040079376 was published Apr. 29, 2004, by Melker, for “Endotracheal tube apparatus and method for using the same to reduce the risk of infections.” A tube-in-tube endotracheal tube apparatus is disclosed.
U.S. Patent Application No. 20050065141 was published Mar. 24, 2005, by Odlink et al., for “Carbapenems useful in treating and preventing pulmonary infections, pharmaceutical compositions thereof and modes of administration thereof.”
Conventional strategies to reduce VAP necessitate purchase of a separate endotracheal tube, which making implementation difficult especially if VAP prevention strategies are to be performed in all settings at the earliest possible time. In addition, each conventional strategy is relatively singular or limited in its ability to prevent VAP.
Also, in a well-known and practiced conventional approach for reducing VAP, nursing and support staff perform repetitive dental and oral hygiene on an intubated patient to attempt to address VAP-causing organisms present in and on the patient's dentition including the gums (gingival) and nearby mucosa. However, this manual hygiene work on intubated patients is labor-intensive, and even so some of them still develop VAP. Use of such techniques in the early stages of intubation such as in the pre-hospital and emergency department settings is not practical. This is unfortunate because these are places where patients are at major risks and where the normal microbial oral flora of the patient rapidly changes to more virulent hospital-based pathogens.